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Biomedical subjects

J W Kemnitz

Publications and source records attributed to J W Kemnitz.

69 records · Page 4Linked to original sources
PubMed1983

Lateral hypothalamic lesions and norepinephrine turnover in rats.

Animals with lateral hypothalamic lesions lost significantly more weight in the 18 h following this lesion than did sham-operated animals or rats with cerebral cortical lesions deprived of food for the same time period. In the acutely fasted sham-operated animals the turnover of norepinephrine in interscapular brown adipose tissue, heart, and pancreas was slowed but in fasted rats with lateral hypothalamic lesions norepinephrine turnover rates were three- to ninefold faster in all three organs. Exposure to the cold (4 degrees C) significantly increased norepinephrine turnover in the interscapular brown adipose tissue, heart, and pancreas of fasted sham-operated rats, but did not further increase the rate of turnover in lateral hypothalamic-lesioned rats. Rats with lesions in the cerebral cortex responded in a fashion similar to that of the sham-operated animals. Gastric erosions and microhemorrhagic gastric mucosa were observed in five of six acutely fasted rats with lateral hypothalamic lesions whereas all sham-operated rats had a normal appearance of the stomach lining. Animals with lateral hypothalamic lesions made 3 wk earlier also showed an increased rate of norepinephrine turnover in the interscapular brown adipose tissue, heart, and pancreas following an 18 h fast. Rats with bilateral lesions in the paraventricular region of the hypothalamus, however, responded similarly to sham-operated animals with a reduction in the turnover in norepinephrine with fasting and an increase in norepinephrine turnover rate after cold exposure even with fasting. These data suggest that lateral hypothalamic lesions produce an acute increase in turnover of norepinephrine, and that this increased turnover persists for up to 3 wk.

Adipose Tissue, Brown↗
PubMed1982

Biochemical and physiological development of fetal rhesus lung.

Study of 17 fetal rhesus monkeys (Macaca mulatta) revealed a sequential rise in lung phosphatidylcholine (PC) concentration due to elevations in both disaturated (DSPC) and unsaturated constituents. The % DSPC in lung tissue clinical abruptly at 145 days of gestation prior to significant increases in PC or DSPC concentration but in association with improved lung deflation stability (% V10). This suggests that the DSPC-to-PC ratio may be a sensitive biochemical indicator of surfactant phospholipid production in lung parenchyma. Phosphatidyl-glycerol content did not increase significantly until after 155 days gestation, which was coincident with maximizing pulmonary distensibility (V max). Declining levels of phosphatidylethanolamine and sphingomyelin in lung tissue at 162 days support the hypothesis that preferential synthesis of PC occurs during late gestation. A serial decline in lung glycogen content with advancing gestation may reflect glycogen utilization as a substrate for lung phospholipid production. Comparison of biochemical and physiological data confirms the impression that discordances occur among lung maturational events. Lastly, a relationship between rising fetal blood cortisol levels and indices of fetal lung development was not demonstrated.

Animals↗
PubMed1982

Complications of pregnancy and fetal development.

Although the outcome of pregnancy for women with diabetes mellitus has improved in recent years, the infant of the diabetic mother has an increased risk of major clinical problems, particularly in the early neonatal period. These include birth injury due to macrosomia, neonatal hypoglycemia, respiratory distress syndrome, and serious congenital anomalies. Because of the great difficulties encountered during attempts to investigate these problems in clinical research protocols, there is a continuing need to establish appropriate animal models of the diabetic pregnancy. Studies carried out over the past decade, primarily with chemically-induced diabetes have suggested techniques which might be useful. In general, the choice of the animal to be studied will depend on the hypotheses being addressed. For instance, small animals such as rabbits and rats made diabetic with streptozotocin have been successfully used for investigation of fetal lung development. Furthermore, the rat model has been helpful for evaluation of fetal anomalies associated with maldevelopment of the spine and central nervous system. Larger animals, such as the nonhuman primate, are more appropriate for studying placental function and amniotic fluid composition in diabetic pregnancies. The task group on pregnancy and fetal development recommends that animal models of diabetes mellitus be used for a more extensive hormonal and metabolic characterization of diabetic mothers during pregnancy, for investigation of placental physiology with respect to the transfer of substrates from mother to fetus, for systematic and comprehensive study of mechanisms controlling fetal lung development, and for delineation of the pathophysiology of neonatal hypoglycemia. It is further recommended that animal models of spontaneous diabetes such as the BB/W rat be used in future studies dealing with pregnancy and fetal development. Because females with spontaneous diabetes show reduced conception rates, there is a pressing need to enhance the fertility of these animals in order to intensify studies on fetal development.

Alloxan↗
PubMed1981

Use of 6-hydroxydopamine to deplete brain catecholamines in the rhesus monkey: effects on urinary catecholamine metabolites and behavior.

The purpose of this study was to determine: 1) whether 6-hydroxydopamine (6-OHDA), previously shown to deplete brain catecholamines (CA) in rodents, depletes brain CA in rhesus monkeys; 2) whether depletion of brain CA produces changes in behavior; and, 3) whether urinary output of 3-methoxy-4-hydroxyphenylglycol (MHPG) reflects brain norepinephrine (NE) depletions. Repeated intracerebroventricular (ICV) injection of 6-OHDA (N = 20; 15.5-73.3 mg/subject) produced chronic changes in social behavior and, at higher dosages, reduced output of urinary MHPG. However, 4 weeks after the last ICV 6-OHDA injection, urinary MHPG excretion returned to baseline values and whole brain CA content was not reliably different from control. A single treatment with 6-OHDA microinjected into the substantia nigra (SN) (N = 12; 120-240 microgram/subject) produced chronic whole brain depletions of brain CA without depleting serotonin. Reductions in brain CA were associated with a specific set of motor behaviors, aphagia, and adipsia. SN 6-OHDA produced greater brain NE depletions than ICV 6-OHDA, but urinary MHPG output was not reduced. SN 6-OHDA treated subjects showed chronic changes in social behavior and were more sensitive to the operant response rate decreasing effects of alpha-methyl-para-tyrosine (AMPT) than control subjects. Subjects with the largest depletions of brain dopamine (DA) (greater than 90%) were hypokinetic, rigid, and had a distal limb tremor. These results show that SN but not ICV injection of 6-OHDA can deplete brain CA in the rhesus monkey. The most prominent behavioral changes were characterized by disturbances in motor function. Urinary MPHG output does not reflect depletions of brain NE in this species.

Animals↗
PubMed1980

Reduced forebrain norepinephrine in rhesus monkeys made obese by hypothalamic lesions.

Young adult male rhesus monkeys received bilateral lesions in the anteromedial lateral hypothalamus. During the year of observation following surgery the animals were hyperphagic and became markedly obese. The mean increase in body weight averaged 66% more for the experimental animals than for the controls. Analyses of catecholamine concentrations in 12 brain regions at the time of sacrifice revealed consistently lower concentrations of norepinephrine (averaging 51% of control) in the frontal cortex of the obese animals as well as a more variable decrease in norepinephrine in the caudate and striatum. There was no consistent effect of the lesions on dopamine in any of the regions studied. There was no obvious relationship between regional catecholamine levels and weight gain within the experimental group.

Animals↗
PubMed1979

Body weight and body composition of male rats following hypothalamic lesions.

Carcass analyses were performed on 160 male rats maintaining reduced, normal, or elevated levels of body weight following lateral hypothalamic (LH), sham (control), or ventromedial hypothalamic (VMH) lesions, respectively. Extracted body lipid (ranging from 26 to 738% of the control mean) correlated highly (r = +0.95) with the level of maintained body weight (which ranged from 67 to 191% of control). Neither the nonfat solids (which ranged from 60 to 123% of control) contributed significantly to the variance in body weight (r = +0.01 and +0.06, respectively). Fat thus accounted for approximately 90% of the overall variance in body weight among LH, control, and VMH animals. Consideration of only the LH data, however, revealed a breakdown of this close covariance of body fat and weight. Fat mass correlated significantly with body weight in LH rats maintaining weight 0-12% below normal; but, at maintained body weights below 88%, the correlation between weight and fat in LH rats was only +0.07. Variation in lean body mass then better accounted for differences in body weight. The implications of these observations for existing lipostatic theories of weight regulation are discussed.

Animals↗
PubMed1977

Effects of gonadectomy on hypothalamic obesity in male and female rats.

The effects of ventromedial hypothalamic (VMH) lesions on body weight, body composition, and food intake were examined in gonadally intact and gonadectomized adult rats of both sexes. The most striking finding was that, while gonadectomy only modestly augmented the weight gain following VMH lesions in females, castrated VMH males gained twice as much weight as gonadally intact VMH males. Furthermore, the weight gain of the castrated VMH males was comparable to that seen in VMH females. Thus, castration of males eliminates the sex difference in body weight gain that is ordinarily observed in gonadally intact animals following VMH lesions. The degree of weight gain in all VMH animals correlated highly with the amount of food eaten, and additional body weight of all VMH animals was accounted for by increased body fat.

Adipose Tissue↗
PubMedDate not supplied

Use of pneumoencephalography to increase stereotaxic accuracy in rhesus monkeys.

A radiographic method for visualizing intracranial structures for stereotaxic surgery is described. The procedure circumvents the problems associated with the use of radiopaque dyes, and it does not require modification of standard stereotaxic equipment. Anatomical data derived from the use of the method are presented, as well as an example of its application for accurately placing cannulae in the midbrain.

Age Factors↗
PubMedDate not supplied

Assessing insulin sensitivity in the cat: evaluation of the hyperinsulinemic euglycemic clamp and the minimal model analysis.

Current methods of assessing glucose tolerance in the cat are inadequate for quantifying insulin sensitivity. The hyperinsulinemic euglycemic clamp (EGC) and the minimal model analysis (MMA) of the frequently sampled intravenous glucose tolerance test (FSIGT) have been used in other species to assess the effects of insulin on glucose homeostasis. Each of these procedures was performed on healthy cats, two weeks apart, to generate indices of insulin sensitivity - M/I (amount of glucose metabolised per unit of plasma insulin concentration) from the EGC and S(I) (insulin sensitivity) from the MMA. Close and significant correlation between M/I and S(I) in individual cats was found (r=0.91, P=0.032). Use of these research methods may further our understanding of feline diabetes mellitus and other endocrinopathies.

Animals↗
PubMedDate not supplied

Risk factors for endometriosis in the rhesus monkey (Macaca mulatta): a case-control study.

The autopsy records between 1980 and 1995 of 399 female rhesus monkeys (Macaca mulatta) at the Wisconsin Regional Primate Research Center were examined. Spontaneous endometriosis was found in 81 (20%) of the animals. The mean (+/- SD) ages at death for animals with and without endometriosis were 20.7 +/- 5.5 (range 10-35) and 13.4 +/- 7.7 (range 4-37) years respectively. Many of the animals had been exposed to experimental procedures, including laparoscopies, hysterotomies and oestradiol implants, and these were examined as possible risk factors for endometriosis. Of the 81 affected animals, 62 were matched to unaffected controls for age at death (to within 1 year) and year of death (to within 2 years) and the effect of various factors on the development of endometriosis was determined using conditional logistic regression. Exposure to three or more oestradiol implants or one or more hysterotomies were both significant risk factors, with estimated relative risks of 9.7 (95% confidence interval 2.5-37.2) and 5.8 (95% confidence interval 1.6-20.2) respectively. Animals that had been exposed to one or more laparoscopies showed no increased risk for developing endometriosis. These findings provide insight into the aetiology of the disease in women. ?2P51 4RR00167

Aging↗
PubMedDate not supplied

An experimental model for studies of fetal maldevelopment in the diabetic pregnancy.

Values for plasma glucose and serum insulin in fasting conditions and glucose disappearance rates during an intravenous glucose tolerance test were obtained from 54 adult female rhesus monkeys. Some of these animals were subsequently made diabetic by intravenous infusion of streptozotocin (STZ). A single treatment with STZ (47.5 mg/kg) was consistently effective in ten animals for inducing severe hyperglycemia and diminished insulin response to glucose infusion. One of four additional animals became significantly glucose intolerant after a single treatment with STZ (30 mg/kg) and three of three animals became glucose intolerant after two treatments at this dosage. The greater effectiveness of STZ for inducing severe diabetes mellitus in the present study compared with previous investigations using nonhuman primates was attributed to rapid mixing and infusion of STZ with proven diabetogenic activity. Severely diabetic animals have been successfully maintained by daily subcutaneous injections of a combination of NPH and regular insulin. Fetuses of monkeys treated with STZ before conception were hyperglycemic and hyperinsulinemic, and four of these six fetuses were large for gestational age. Preliminary data suggest that fetal lung glycogen concentrations were elevated in these animals compared with controls at 145 days of gestation. It is concluded that the rhesus monkey treated with STZ before pregnancy represents a useful model for studies of fetal maldevelopment in pregnancies complicated by varying degrees of maternal diabetes.

Animals↗
PubMedDate not supplied

Hypocholesterolemic effect of exogenous dehydroepiandrosterone administration in the rhesus monkey.

The effect(s) of exogenous dehydroepiandrosterone (DHEA) was studied in healthy non-obese rhesus monkeys. Six monkeys were given 60 mg/kg/day DHEA for 4 weeks. The dose was then increased to 75 mg/kg/day for an additional 4 weeks. Another six monkeys were given placebo, daily for 8 weeks. Body weight, activity level, average daily food intake, and plasma T4, insulin, total androgen and cortisol concentrations remained unchanged for all 12 monkeys throughout the 8 weeks. Both groups had a significant (p < 0.05) decrease in total plasma cholesterol, however the DHEA treated monkeys were significantly lower than the placebo monkeys. The change in cholesterol in the DHEA treated group primarily affected the fraction containing the low density lipoprotein cholesterol which remained overall unchanged for the placebo monkeys. Both groups had a decrease in high density lipoprotein cholesterol, however there was no difference between the treatment groups. We conclude that in the rhesus monkey, exogenous administration of DHEA acutely reduces cholesterol concentration, particularly the lipoprotein fraction containing low density lipoprotein, without changing food intake, activity level, or body weight.

Animals↗
PubMedDate not supplied

The effect of high fat diet and dehydroepiandrosterone (DHEA) administration in the rhesus monkey.

Dehydroepiandrosterone (DHEA) lowers serum cholesterol, particularly the low density lipoprotein (LDL) fraction, in rhesus monkeys on a commercial diet (12% calories from fat, 0.0083% cholesterol). We fed rhesus monkeys a diet of 30% calories from fat and 0.1% cholesterol for 12 weeks, then commercial chow for 7 weeks. Six monkeys each received DHEA or placebo, orally for 17 weeks. Food intake increased the first 6 weeks, but decreased thereafter. Monkeys had a 22% mean weight gain while on high fat diet. DHEA monkeys had higher T4 levels than placebo monkeys at weeks 8 and 16. After 12 weeks on high fat diet, all monkeys had elevated serum cholesterol concentrations, an increase in amount and percentage of intermediate density lipoprotein and LDL cholesterol, and an increase in amount, but a decrease in percentage of high density lipoprotein cholesterol. There were no significant differences in serum cholesterol or plasma lipoprotein concentrations between DHEA and placebo monkeys while on high fat diet (a trend toward lower levels was noted in the DHEA group). On commercial chow, plasma lipoprotein concentrations decreased for all monkeys, and DHEA monkeys had significantly lower total and LDL cholesterol than placebo monkeys. We conclude that a high fat diet (30% fat) masks any cholesterol-lowering effects of DHEA.

Administration, Oral↗